Cannabinoids are terpenophenolic compounds found in Cannabis sativa, an annual plant belonging to the Cannabaceae family. The plant contains more than 400 chemicals and approximately 70 cannabinoids, which accumulate mainly in the glandular trichomes. The main psychoactive cannabinoid is tetrahydrocannabinol (THC) or more precisely its main isomer (−)-trans-Δ9-tetrahydrocannabinol ((6aR,10aR)-Δ9-tetrahydrocannabinol), which is used for treating a wide range of medical conditions, including glaucoma, AIDS wasting, neuropathic pain, treatment of spasticity associated with multiple sclerosis, fibromyalgia and chemotherapy-induced nausea. THC is also effective for treating allergies, inflammation, infection, epilepsy, depression, migraine, bipolar disorders, anxiety disorder, drug dependency and drug withdrawal syndromes.
In addition to THC, other biologically active cannabinoids are also present in C. sativa plant. One such cannabinoid is cannabidiol (CBD), an isomer of THC, which is a potent antioxidant and anti-inflammatory compound known to provide protection against acute and chronic neuro-degeneration. Another biologically active cannabinoid is cannabigerol (CBG). CBG is found in high concentrations in hemp. It is a high affinity α2-adrenergic receptor agonist, a moderate affinity 5-HT1A receptor antagonist and is a low affinity CB1 receptor antagonist. CBG is known to possess a mild anti-depressant activity. Cannabichromene (CBC) is another biologically active cannabinoid and is known to possess anti-inflammatory, anti-fungal and anti-viral properties. Although many phytocannabinoids are biologically active against the above mentioned disease conditions, the acceptance of phytocannabinoids as candidate therapeutic agents for treating such disease conditions has been slow due to their addictive nature.
Accordingly, efforts have been made to identify phytocannabinoids that retain one or more of the therapeutic properties described above but lack the addictive properties. In this regard, it is known that tetrahydrocannabinolic acid (THCA) and cannabivarin (cannabivarol or CBV) are non-psychoactive, while phytocannabinoids such as tetrahydrocannabivarin (THC-v or THV) and cannabionol (CBN) show mild psychoactive properties.
The naturally low amounts of THC-v, CBV and CBN in the hemp plant Cannabis sativa is one important reason why research characterizing the therapeutic and physchoactive properties of these cannabinoids is slow. Additionally, not much is known about the biosynthesis of these cannabinoids or why they are produced at such low levels in the hemp plant.
The present invention addresses many of these questions and provides a method for the bioenzymatic manufacture of THC-v, CBN and CBV and further provides methodologies for the large-scale production of these cannabinoids for therapeutic use.